Unwanted immune responses are involved in various disorders. Examples of these disorders include adverse drug reactions (ADRs), graft-versus-host diseases (GVHD), inflammatory diseases, autoimmune diseases, transplant rejection, allergic diseases, and T cell-derived cancers. All of them are major clinical problems.
For example, ADRs account for 6-7% of all hospital admissions and remain. Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening cutaneous ADRs characterized by massive keratinocyte apoptosis. These two disorders are considered to be variants of the same disease with different severity as both are characterized by a rapidly developing blistering exanthema of purpuric macules and target-like lesions accompanied by mucosal involvement and skin detachment to a varying extent (Roujeau et al., N. Engl. J. Med. 1994 Nov. 10; 331(19):1272-85). SJS is defined as skin detachment of less than 10%, TEN as greater than 30%, and overlapping SJS/TEN as 10-30% (Roujeau et al., J. Invest. Dermatol. 1994 June; 102(6):285-305). The histopathology observations of SJS and TEN include marked keratinocyte apoptosis in the epidermis with dermo-epidermal separation and epidermal necrosis, resulting in bullae and extensive mucocutaneous shedding Paul et al. Br. J. Dermatol. 1996 April; 134(4):710-4. Besides the severe cutaneous manifestations, SJS/TEN may be accompanied by fever, myocarditis, myocardial infarction, hepatitis, acute renal failure, and affect respiratory and gastrointestinal systems. Although the incidence of SJS/TEN is low, these conditions can kill or severely disable previously otherwise healthy people. A few cases have prompted the pharmaceutical companies' withdrawal of newly released drugs (Roujeau et al., N. Engl. J. Med. 1994 Nov. 10; 331(19):1272-85).
There is a need for methods to diagnose or treat diseases associated with unwanted immunological responses.